Mitochondrial Energy Homeostasis and Quality Control: Mechanistic Insights and Therapeutic Avenues in Aging

The process of aging is fundamentally intertwined with mitochondrial dysfunction, characterized by a progressive decline in both energy production and the maintenance of mitochondrial integrity. As the cell’s primary energy-producing organelles, mitochondria exhibit age-associated impairments in oxidative phosphorylation, ATP synthesis, and metabolic adaptability. This deterioration is often accompanied by increased production of reactive oxygen species, which exacerbates oxidative damage and contributes to cellular and tissue dysfunction. Importantly, mitochondrial dysfunction is increasingly recognized not merely as a byproduct of aging, but as an active driver of physiological decline and the onset of age-associated diseases, including neurodegenerative and metabolic disorders. While significant progress has been made in elucidating mitochondrial impairments, key questions remain regarding the primary drivers of mitochondrial decline and the feasibility of targeted therapeutic interventions.A critical area within this field is mitochondrial quality control (MQC), which encompasses a coordinated set of processes - including mitophagy, mitochondrial dynamics, proteostasis, and biogenesis. These processes collectively maintain a functional mitochondrial network throughout life. However, accumulating evidence suggests that these quality control systems become progressively compromised with age, leading to the accumulation of dysfunctional mitochondria and subsequent energetic failure. Although interventions such as caloric restriction, pharmacological modulation, and gene-editing approaches have shown promise in restoring mitochondrial homeostasis in experimental models, important questions remain regarding their mechanistic basis, tissue specificity, and translational potential. A comprehensive understanding of how MQC intersects with mitochondrial energy decline, as well as the identification of optimal therapeutic targets, is still lacking.This Research Topic aims to advance our understanding of the interplay between mitochondrial energy homeostasis and cellular quality control mechanisms in aging. Specifically, it seeks to elucidate how these interconnected processes contribute to functional decline at the cellular, tissue, and organismal levels, to clarify their roles in the pathogenesis of age-related diseases, and to explore potential interventions that may improve healthspan or mitigate disease progression. The overarching goal is to stimulate discussion, accelerate discovery, and inspire innovative strategies for maintaining mitochondrial health across the lifespan.This Research Topic will primarily focus on mechanistic, translational, and therapeutic aspects of mitochondrial dysfunction in aging, with particular emphasis on energy homeostasis and quality control pathways. Studies addressing additional regulatory mechanisms or inter-organelle signaling are also welcome, provided they are directly related to mitochondria-associated decline during aging. To further advance this field, we invite submissions addressing, but not limited to, the following topics:- Bioenergetics & Metabolism: Mitochondrial energy collapse and metabolic reprogramming during aging.- Mechanisms of MQC: Molecular pathways governing mitophagy, mitochondrial dynamics (fission/fusion), and proteostasis.- Organelle Crosstalk: Interactions between mitochondria and other cellular compartments in the context of age-related decline.- Translational & Cutting-edge Interventions: Genetic, pharmacological, and lifestyle strategies to restore mitochondrial homeostasis. We particularly welcome studies on emerging therapies such as mitochondrial transplantation, senolytics targeting mitochondria, and the application of artificial intelligence in mitochondrial modelling.- Systems Biology, Multi-omics & Biomarkers: Integrative approaches including multi-omics integration (transcriptomics, proteomics, and metabolomics) to identify biomarkers of mitochondrial dysfunction and energetic failure. Topic editors: Jiahuan He, Pengbo Wang, Lei Wang Source: https://www.frontiersin.org/research-topics/83079/mitochondrial-energy-homeostasis-and-quality-control-mechanistic-insights-and-therapeutic-avenues-in-aging